A5056857839- Ubiquitin and proteasome pathways
- Effects of Radiation Exposure
- Carcinogens and Genotoxicity Assessment
- Radiation Effects and Dosimetry
- Protein Degradation and Inhibitors
- Neuroscience and Neural Engineering
- Peptidase Inhibition and Analysis
- Nuclear and radioactivity studies
- Radiation Therapy and Dosimetry
- Cancer-related Molecular Pathways
- Click Chemistry and Applications
- Autophagy in Disease and Therapy
- Radioactivity and Radon Measurements
- Advanced Memory and Neural Computing
- Histone Deacetylase Inhibitors Research
- Carbon dioxide utilization in catalysis
- Orthopaedic implants and arthroplasty
- Pharmacovigilance and Adverse Drug Reactions
- Silk-based biomaterials and applications
- bioluminescence and chemiluminescence research
- Pesticide Exposure and Toxicity
- Plant Toxicity and Pharmacological Properties
- Signaling Pathways in Disease
- Calcium signaling and nucleotide metabolism
- Hydrogen's biological and therapeutic effects
Almac (United Kingdom)
2011-2024
Rowan University
2021-2024
Hobart Private Hospital
2018
Guy's and St Thomas' NHS Foundation Trust
2017
Queen's University Belfast
2007
National Cancer Institute
1972-2003
Molecular Oncology (United States)
2002-2003
Abstract Background Understanding how to modulate the microenvironment of tumors that are resistant immune checkpoint inhibitors represents a major challenge in oncology.Here we investigate ability USP7 reprogram tumor (TME) by inhibiting secretion vascular endothelial growth factor (VEGF) from fibroblasts. Methods To understand role played TME, systematically evaluated effects potent, selective on co‐cultures comprising components using human primary cells. We also inhibition syngeneic...
During the 1991 Persian Gulf War several US military personnel were wounded by shrapnel fragments consisting of depleted uranium. These treated as conventional and not surgically removed to spare excessive tissue damage. Uranium bioassays conducted over a year after initial uranium injury indicated significant increase in urine levels above natural background levels. The potential mutagenic effects are unknown. To assess long-term exposure internalized uranium, Sprague-Dawley rats implanted...
Ubiquitin specific protease 7 (USP7, HAUSP) has become an attractive target in drug discovery due to the role it plays modulating Mdm2 levels and consequently p53. Increasing interest USP7 is emerging its potential involvement oncogenic pathways as well possible roles both metabolic immune disorders addition viral infections. Potent, novel, selective inhibitors of have been developed using rational structure-guided design enabled by high-resolution cocrystallography. Initial hits were...
Limited data exist to permit an accurate assessment of risks for carcinogenesis and mutagenesis from embedded fragments or inhaled particulates depleted uranium (DU). Ongoing studies have been designed provide information about the carcinogenic potential DU using in vitro vivo assessments morphological transformation as well cytogenetic, mutagenic, oncogenic effects. For comparison, we also examined tungsten alloys used military projectiles known carcinogen nickel. Quantitative qualitative...
The acute effects of whole-body irradiation and the pattern recovery from sublethal radiation injury can only be estimated for human beings scattered highly unusual exposure situations. These situations include atomic bomb detonations in Japan, nuclear reactor accidents, organ transplantation studies. are little value these purposes because uncertain dose estimates, complicating thermal burns, insufficient mortality records. Estimates LD50 based on data accidents contribute information there...
Abstract The serine/threonine protein kinase AKT plays a pivotal role within the PI3K pathway in regulating cellular proliferation and apoptotic functions, hyper-activation via gene amplification and/or mutation has been implicated multiple human malignancies. There are 3 isoenzymes (AKT1-3) which mediate critical, non-redundant functions. We present discovery development of ALM301, novel, allosteric, sub-type selective inhibitor AKT1/2. ALM301 binds an allosteric pocket created by combined...
Abstract : Radiation lethality has been studied with Co60 gamma radiation at five exposure rates ranging from 660 to 2.0 R/hr. The data show that a decrease in the exposure-rate (or protracting over longer time periods) results an increase LD50, e.g., LD50 R/hr is 237 R while it 637 R. An analysis of these linearity through range - 30 However, between and 3.6 R/hr, sharp departure this relationship occurs LD50's being considerably higher than would be predicted extrapolation. In another...
Abstract : A modified split-dose technique was used to measure the accumulation of injury during protracted exposures domestic sheep Cobalt-60 gamma radiation. An initial or conditioning exposure 165 R given at 0.5, 0.95, 1.85, and 3.94 R/hr, acute LD50/60 determined immediately thereafter. These studies indicate that there is a dose rate threshold for under these conditions irradiation lies between 1.0 1.5 R/hr. Recovery from accumulated has been studied by determining various times after...
Abstract Cancer cachexia is a metabolic wasting syndrome characterized by weight loss, anorexia and anemia as result of tumor burden, affects up to 80% advanced cancer patients #1. Cachexia particularly prevalent in pancreatic, lung, colorectal gastro-intestinal cancers can lead reduced tolerance responsiveness chemotherapy, increased treatment-related toxicity morbidity, poor overall quality life. There are currently no approved therapies for cachexia. The development maintenance muscle...
Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, 46 mg/kg-day, 90 1, 5, 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but toxicity, the higher doses, was evident by: 1) losses body weight gain organ weights, 2) reductions food consumption, 3) hematological microscopic examinations both study periods. Significant decreases erythrocyte count, hemoglobin, hematocrit were found...
Abstract : Dose distributions with depth in a dog cadaver and cylindrical phantom have been obtained for 1 Mvp transmitted X rays mixed neutron gamma radiation from reactor. The ratio of to dose was 4:1 at the surface dog. Measurement or X-ray made using LiF thermoluminescence dosimeters, while activation small sulfur pellets, suitable calibrations. Placement dosimeters verified by roentgenography. Penetration is considerably higher than that reactor neutrons, whose effective energy about...
Ovarian cysts are a common pathology in women of all age groups. It is estimated that 5-10% have surgical intervention to remove an ovarian cyst their lifetime. Given this frequency rate, characterization masses essential for optimal management patients. Patients with benign can be managed conservatively if they asymptomatic. Mature teratomas occur, most cases, premenopausal women. These contain different types human tissue including bone, cartilage, fat, hair, or other tissue. If causing no...
Abstract This study reports ambient electrosynthesis of dimethyl carbonate with a palladium–gold catalyst. Material screening identifies region intermediate‐catalyst binding energy that facilitates interfacial electron and proton transfers for selective carbonylation, achieving distinct maximum 92% faradaic efficiency to carbonate. Structural electrochemical analyses suggest the alloying palladium gold effectively modulates CO* catalytic surface, in accord subsequent computational studies....
Although numerous studies have been conducted to describe injury accumulation and recovery in several mammalian species during after exposure ionizing radiation, the characterization of time-course curve for repair has never fully resolved. It suggested by Blair, 2 that, radiation injury, rate animals increases exponentially with time. Extensive data Sacher (1, 2) Grahn (3) indicate that mouse goes through a series maxima at specific time intervals which correspond intestinal bone marrow...